A unique, highly polymorphic dopamine receptor gene, DRD4, was previously identified, cloned, and sequenced. DRD4 has eight known alleles, each varying in size by a repeating motif of 48 base pairs in Exon III. Each repeating motif adds 16 amino acids to the intracytoplasmic loop, which is responsible for G-protei binding. The DRD4.7 (seven repeat) allele has altered ligand affinity and salt sensitivity. DRD4 is an intriguing candidate for genetic variations in dopamine-related behaviors, such as reward seeking behaviors and movement disorders. We estimated DRD4 allele frequencies in a well-characterized population of Finnish alcoholics and controls and in four other populations of alcoholic and ethnically matched control subjects: Blacks, Pima Indians, Cheyenne Indians, and Jemez-Pueblo Indians. Many of the Finnish alcoholics were of the early onset, impulsive type. No association between a particular DRD4 allele or DRD4 genotype and alcoholism was observed, nor was there an association with CSF homovanillic acid, an indicator of central dopaminergic function. Interpopulation variation in frequencies of DRD4 alleles and genotypes was found. Use of SSCP to detect sequence variation within the repeating 48 bp segments may elucidate whether the population differences in alleles and genetypes are behaviorally significant.